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      Metabolic Effects of Insulin-Like Growth Factor I in Normal Humans

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          Abstract

          Since the development of recombinant DNA technology, there has been a rapid expansion of interest in the use of human insulin-like growth factor I (IGF-I) synthesized by recombinant DNA technology for the treatment of clinical disorders. This article reviews recent studies of the metabolic effects of recombinant human IGF-I in normal humans. These studies demonstrated that under euglycemic conditions, IGF-I had potent effects on glucose (hepatic and peripheral), lipid and amino acid metabolism that closely resemble those of insulin, despite a concomitant inhibitory effect on insulin secretion. Hypoglycemia produced by IGF-I infusions (free-fall study and glucose clamps) had a different effect on counterregulatory responses compared with insulin. The glucagon response was absent, growth hormone (GH) release was attenuated, while norepinephrine levels were increased. Suppression of glucagon release during hypoglycemia impaired glucose recovery. Paradoxically, awareness of hypoglycemia was enhanced with IGF-I, partly due to stimulation of sympathetic activity. Studies performed under hyperglycemic conditions showed that IGF-I inhibited glucose-stimulated insulin secretion, but that this inhibitory effect was partially overcome by increasing the hyperglycemic stimulus. Moreover, despite the decrease in insulin secretion, glucose disposal was accelerated by IGF-I. These observations imply that IGF-I might be effective in human diabetes. In particular, normalization of the decreased basal IGF-I levels, which are characteristic of poorly controlled patients with insulin-dependent diabetes mellitus (IDDM), in pubertal patients might lower glucagon and GH levels and improve cellular metabolism in muscle. Further studies are necessary, however, to determine whether IGF-I has a therapeutic role in this group of patients with IDDM who are particularly difficult to treat with insulin.

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          Author and article information

          Journal
          HRE
          Horm Res Paediatr
          10.1159/issn.1663-2818
          Hormone Research in Paediatrics
          S. Karger AG
          978-3-8055-6003-0
          978-3-318-00608-7
          1663-2818
          1663-2826
          1994
          1994
          05 December 2008
          : 41
          : Suppl 2
          : 97-102
          Affiliations
          Departments of Internal Medicine and Pediatrics, Yale University School of Medicine, New Haven, Conn., USA
          Article
          183968 Horm Res 1994;41:97–102
          10.1159/000183968
          8088711
          © 1994 S. Karger AG, Basel

          Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

          Page count
          Pages: 6
          Categories
          Symposium Session II: Hormone Receptor Physiology and Novel Therapeutic Approaches

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